OVERALL ABSTRACT The use of antiretroviral therapy to turn HIV infection into a chronic disease has been a major medical advancement. However, along with this has been the recognition of sequelae of HIV as a chronic condition, with end-organ consequences such as the HIV-associated neurocognitive disorder (HAND), as the brain is a target of HIV, and interactions with disease associated with aging. Indeed, the face of HIV infection is changing to an older population, and soon over half of infected individuals in the U.S. will be 50 years of age or greater. As age is the largest risk factor for neurodegenerative diseases, this graying of the HIV pandemic is a critical focus of study especially for the central nervous system. Furthermore, the brain can provide a reservoir for HIV, impacting efforts to find a functional cure. NIH P30 Centers support shared resources and facilities for research in a focused field. Here, we propose to build upon striking successes we have made in multiple areas to continue the UNMC Chronic HIV Infection and Aging in NeuroAIDS (CHAIN) Center. We have revised the Center based on our findings and current issues and needs in the field, and these closely follow the new NIH priority topics for using AIDS-designated funds, including neurological complications, comorbidies, cross-cutting basic research, long-acting therapeutics, and reservoir and cure. Through this Center mechanism, we will significantly facilitate research and accomplishments across these areas. Experts in a number of fields will direct Imaging, Therapeutics, Cell- Tissue-Animal, and Omics Cores. These, combined with a Developmental Core to stimulate new and innovative work and an Administrative Core to integrate and run the Center, will serve to significantly enhance our knowledge of neuroAIDS, its prevention and treatment, while joining others in work for an overall cure for HIV.